Heart failure potentially affects the cortical structure of the brain.

BACKGROUND: Heart failure (HF) has been reported to affect cerebral cortex structure, but the underlying cause has not been determined. This study used Mendelian randomization (MR) to reveal the causal relationship between HF and structural changes in the cerebral cortex. METHODS: HF was defined as the exposure variable, and cerebral cortex structure was defined as the outcome variable. Inverse-variance weighted (IVW), MR-Egger regression and weighted median (WME) were performed for MR analysis; MR-PRESSO and Egger's intercept was used to test horizontal pleiotropy; and "leave-one-out" was used for sensitivity analysis. RESULTS: Fifty-two single nucleotide polymorphisms (SNPs) were defined as instrumental variables (IVs), and there was no horizontal pleiotropy in the IVs. According to the IVW analysis, the OR and 95% CI of cerebral cortex thickness were 0.9932 (0.9868-1.00) (P=0.0402), and the MR-Egger intercept was -15.6× 10-5 (P = 0.7974) and the Global test pval was 0.078. The P-value of the cerebral cortex surface was 0.2205, and the MR-Egger intercept was -34.69052 (P= 0.6984) and the Global Test pval was 0.045. HF had a causal effect on the surface area of the caudal middle frontal lobule (P=0.009), insula lobule (P=0.01), precuneus lobule (P=0.049) and superior parietal lobule (P=0.044). CONCLUSIONS: HF was potentially associated with changes in cortical thickness and in the surface area of the caudal middle frontal lobule, insula lobule, precuneus lobule and superior parietal lobule.

The Efficacy of Machine Learning Models for Predicting the Prognosis of Heart Failure: A Systematic Review and Meta-Analysis.

INTRODUCTION: Heart failure (HF) is a major global public health concern. The application of machine learning (ML) to identify individuals at high risk and enable early intervention is a promising approach for improving HF prognosis. We aim to systematically evaluate the performance and value of ML models for predicting HF prognosis. METHODS: PubMed, Web of Science, Scopus, and Embase online databases were searched up to April 30, 2023, to identify studies on the use of ML models to predict HF prognosis. HF prognosis primarily encompasses readmission and mortality. The meta-analysis was conducted by MedCalc software. Subgroup analyses include grouping based on types of ML models, time interval, sample sizes, the number of predictive variables, validation methods, whether to conduct hyperparameter optimization and calibration, data set partitioning methods. RESULTS: A total of 31 studies were included. The most common ML models were random forest, boosting, support vector machine, neural network. The area under the receiver operating characteristic curve (AUC) for predicting HF readmission was 0.675 (95% CI 0.651-0.699, P<0.001), and the AUC for predicting HF mortality was 0.790 (95% CI 0.765-0.816, P<0.001). Subgroup analyses revealed that models with the prediction time interval of 1 year, sample sizes =10,000, the number of predictive variables =100, external validation, hyperparameter tuning, calibration adjustment, and data set partitioning using 10-fold cross-validation exhibited favorable performance within their respective subgroups. CONCLUSION: The performance of ML models in predicting HF readmission is relatively poor, while its performance in predicting HF mortality is moderate. The quality of the relevant studies is generally low, it is essential to enhance the predictive capabilities of ML models through targeted improvements in practical applications.

Qifu Yixin Formula Improves Heart Failure by Enhancing ß-Arrestin2 Mediated the SUMOylation of SERCA2a.

Purpose: This study aimed to elucidate the protective mechanism of Traditional Chinese Medicine (TCM) Qifu Yixin formula (QFYXF) to improve heart failure (HF) by promoting ß-arrestin2 (ß-arr2)-mediated SERCA2a SUMOylation. Materials and Methods: The transverse aortic constriction (TAC)-induced HF mice were treated with QFYXF or carvedilol for 8 weeks. ß-arr2-KO mice and their littermate wild-type (WT) mice were used as controls. Neonatal rat cardiomyocytes (NRCMs) were used in vitro. Cardiac function was evaluated by echocardiography and serum NT-proBNP. Myocardial hypertrophy and myocardial fibrosis were assessed by histological staining. ß-arr2, SERCA2a, SUMO1, PLB and p-PLB expressions were detected by Western blotting, immunofluorescence and immunohistochemistry. SERCA2a SUMOylation was detected by Co-IP. The molecular docking method was used to predict the binding ability of the main active components of QFYXF to ß-arr2, SERCA2a, and SUMO1, and the binding degree of SERCA2a to SUMO1 protein. Results: The HF model was constructed 8 weeks after TAC. QFYXF ameliorated cardiac function, inhibiting myocardial hypertrophy and fibrosis. QFYXF promoted SERCA2a expression and SERCA2a SUMOylation. Further investigation showed that QFYXF promoted ß-arr2 expression, whereas Barbadin (ß-arr2 inhibitor) or ß-arr2-KO reduced SERCA2a SUMOylation and attenuated the protective effect of QFYXF improved HF. Molecular docking showed that the main active components of QFYXF had good binding activities with ß-arr2, SERCA2a, and SUMO1, and SERCA2a had a high binding degree with SUMO1 protein. Conclusion: QFYXF improves HF by promoting ß-arr2 mediated SERCA2a SUMOylation and increasing SERCA2a expression.

Promyelocytic leukemia zinc finger controls type 2 immune responses in the lungs by regulating lineage commitment and the function of innate and adaptive immune cells.

Type 2 immune responses are critical for host defense, mediate allergy and Th2-high asthma. The transcription factor, promyelocytic leukemia zinc finger (PLZF), has emerged as a significant regulator of type 2 inflammation in the lung; however, its exact mechanism remains unclear. In this review, we summarized recent findings regarding the ability of PLZF to control the development and function of innate lymphoid cells (ILCs), iNKT cells, memory T cells, basophils, and other immune cells that drive type 2 responses. We discussed the important role of PLZF in the pathogenesis of Th2-high asthma. Collectively, prior studies have revealed the critical role of PLZF in the regulation of innate and adaptive immune cells involved in type 2 inflammation in the lung. Therefore, targeting PLZF signaling represents a promising therapeutic approach to suppress Th2-high asthma.

PLZF promotes the development of asthma tolerance via affecting memory phenotypes of immune cells.

Clarifying the pathogenesis of asthma and/or identifying the specific pathway underlying oral asthma tolerance (OT) would be of great significance. In our previous study, promyelocytic leukemia zinc finger (PLZF), which reportedly regulates memory phenotypes, was found to promote ovalbumin (OVA)-induced OT. Therefore, this study aimed to explore the regulatory effects of PLZF on memory phenotypes in asthma and OT mouse models. We found that Zbtb16 (encoding PLZF) and PLZF+ cells were highly increased in OT lungs compared with asthmatic lungs. PLZF was co-expressed with GATA3, and IL-4+PLZF+ cells were significantly lower in OT lungs than in asthmatic lungs. Notably, memory cells were decreased in OT mice, and these mice had PLZF+ cells that expressed lower levels of CD44 than those of asthmatic mice. When Zbtb16 was overexpressed in splenic lymphocytes, the number of CD44+ cells decreased. There were increased memory cells in splenic lymphocytes after treatment with the supernatant of OVA-treated airway epithelial cells; however, this was reversed by Zbtb16 overexpression. Early respiratory syncytial virus infection increased memory cells and reduced PLZF+ cells in the OT mice. Collectively, these results indicate that PLZF may reduce the proportion of memory cells, thereby, promoting the establishment of OT.

CEP55 predicts the poor prognosis and promotes tumorigenesis in endometrial cancer by regulating the Foxo1 signaling.

Endometrial cancer is a common gynecologic cancer, which is relevant to many differentially expressed genes. Centrosomal protein 55 (CEP55) was proved to be aberrantly expressed in several cancers. However, the function of CEP55 in endometrial cancer remains largely uncertain. The differentially expressed genes in endometrial cancer were analyzed by GEO datasets. CEP55 expression and its correlation to aggressive behaviors and diagnosis were analyzed by TCGA and the Human Protein Atlas databases. The association between CEP55 expression and 5-year overall survival in endometrial cancer was predicted using Kaplan-Meier Plotter database. Cell proliferation and apoptosis were determined by western blotting, EdU staining, TUNEL staining, and LDH release. CEP55-related targets were predicted by LinkedOmics and analyzed by KEGG pathway analysis using KOBAS. Foxo1 level was detected by western blotting. CEP55 expression was increased in endometrial cancer. The upregulated CEP55 was associated with tumor invasion, histologic grade, histological type and poor prognosis in endometrial cancer. CEP55 knockdown decreased PCNA and CDK2 levels and inhibited cell proliferation. Moreover, CEP55 downregulation promoted cell apoptosis, LDH release and increased cl-caspase-3/caspase-3 level. CEP55-related targets were enriched in Foxo1 signaling. CEP55 silencing increased the transcription activity of Foxo1. Inhibition of Foxo1 activity reversed the effect of CEP55 knockdown on cell proliferation and apoptosis. In conclusion, CEP55 knockdown repressed cell proliferation and facilitated apoptosis by regulating the Foxo1 signaling in endometrial cancer.

Oral antibiotics relieve allergic asthma in post-weaning mice via reducing iNKT cells and function of ADRB2.

The role of normal gut microbiota in asthma or ovalbumin (OVA)-induced asthma tolerance (OT) remains unclear. Here, we established mouse models of asthma and OT followed by 2 weeks of antibiotic treatment, to clear the gut microbiota. Antibiotic treatment was found to alleviate allergic asthma accompanied with a reduction of invariant natural killer (iNKT) cells. By RNA-seq analysis, we found that ß-adrenergic receptor (ADRB) genes, including Adrb1, Adrb2, and Adrb3, were downregulated in asthmatic lungs, but these changes were reversed in OT lungs. Moreover, Adrb2 and Adrb3 were significantly upregulated in asthmatic lungs after antibiotic treatment. Surprisingly, blocking ADRB with propranolol relieved allergic asthma while reducing T helper 2 (Th2) and Treg cell numbers. Further analyses using flow cytometry and immunofluorescence showed that the protein expression level of ADRB2 was higher in asthmatic lungs than that in the control and OT lungs. Notably, dendritic cells (DCs), especially the ADRB2+ DCs, were increased in asthmatic lungs compared to that in the control and OT lungs. In addition, ADRB2+ DCs were significantly reduced following the administration of the ADRB2-specific antagonist ICI118551. Our findings suggest that antibiotic treatment can alleviate OVA-induced allergic asthma via reducing the frequency of iNKT cells and function of ADRB2.

Pulmonary resident memory T cells in respiratory virus infection and their inspiration on therapeutic strategies.

The immune system generates memory cells on infection with a virus for the first time. These memory cells play an essential role in protection against reinfection. Tissue-resident memory T (TRM) cells can be generated in situ once attacked by pathogens. TRM cells dominate the defense mechanism during early stages of reinfection and have gradually become one of the most popular focuses in recent years. Here, we mainly reviewed the development and regulation of various TRM cell signaling pathways in the respiratory tract. Moreover, we explored the protective roles of TRM cells in immune response against various respiratory viruses, such as Respiratory Syncytial Virus (RSV) and influenza. The complex roles of TRM cells against SARS-CoV-2 infection are also discussed. Current evidence supports the therapeutic strategies targeting TRM cells, providing more possibilities for treatment. Rational utilization of TRM cells for therapeutics is vital for defense against respiratory viruses.

Long noncoding RNA GAS5 attenuates cigarette smoke-induced airway remodeling by regulating miR-217-5p/PTEN axis.

Airway remodeling is a remarkable pathological characteristic of chronic obstructive pulmonary disease (COPD), and long noncoding RNAs have been demonstrated to participate in COPD development and pathogenesis. Here, we investigate the role of long noncoding RNA GAS5 in cigarette smoke (CS)-induced airway remodeling. GAS5 expression is significantly lower in lung tissues of CS-exposed mice than in tissues of control mice without exposure to CS. Forced GAS5 overexpression suppresses CS-induced airway inflammation and remodeling. GAS5 overexpression also inhibits CS extract-induced inflammatory-cytokine expression and fibroblast activation in vitro. Regarding the mechanism, GAS5 acts as a sponge of miR-217-5p, thereby increasing PTEN expression. MiR-217-5p overexpression and PTEN knockdown separately reverse the inhibitory effects of GAS5 overexpression on the inflammatory-cytokine expression and fibroblast activation. Collectively, these results suggest that GAS5 can suppress airway inflammation and fibroblast activation by regulating miR-217-5p/PTEN axis, which may help develop novel therapeutic strategies against COPD.

Suppression of circXPO1 attenuates cigarette smoke-induced inflammation and cellular senescence of alveolar epithelial cells in chronic obstructive pulmonary disease.

Smoking is an essential facet of the pathogenesis of chronic obstructive pulmonary disease (COPD), which is typically characterized by inflammation and cellular senescence of alveolar epithelial cells. In this study, we investigated the function and fundamental mechanism of a novel circular RNA XPO1 (circXPO1) in cigarette smoke (CS)-induced inflammation and cellular senescence of alveolar epithelial cells. We found that circXPO1 was overexpressed in the lungs of CS-exposed mice and the CS extract (CSE)-treated alveolar epithelial cell line MLE12. Suppression of circXPO1 inhibited CSE-induced inflammatory cytokine production and cellular senescence. In vivo assays also demonstrated that circXPO1 knockdown attenuates CS-induced inflammation and senescence in the mouse lungs. Mechanistically, circXPO1 can directly bind to miR-23b-3p, preventing miR-23b-3p from binding to its target TGF-ß-activated kinase 1/MAP3K7 binding protein 3 (TAB3)mRNA. In addition, under CSE conditions, miR-23b-3p overexpression recapitulated the prophylactic effects of circXPO1 knockdown. Inhibition of miR-23b-3p attenuated the function of circXPO1 knockdown in CSE-treated MLE12 cells. These results reveal that circXPO1 plays a role in the pathogenesis of COPD by modulating TAB3 through sponging miR-23b-3p.

Case Report: Rare Dynein Axonemal Heavy Chain 9 Mutations in a Han-Chinese Patient With Kartagener Syndrome.

A 52-year-old woman presented with respiratory symptoms of productive cough and shortness of breath. She had suffered from repeated pneumonia. The CT scans revealed chronic sinusitis, tree bud signs in pulmonary imaging, and situs inversus. She received a primary diagnosis of Kartagener syndrome of primary ciliary dyskinesia (PCD) and a genetic examination was performed. Compound heterozygous mutations in dynein axonemal heavy chain 9 (DNAH9) were identified, which encoded outer dynein arms (ODAs) components. DNAH9 mutations are relatively rare events in PCD, and this is the first report of PCD patients with DNAH9 mutations in the Chinese population. Further, a literature review of mutations in PCD was conducted.

Hematological characteristics of patients with novel coronavirus pneumonia in intensive care unit.

BACKGROUND: Toward the end of December 2019, a novel type of coronavirus (2019-nCoV) broke out in Wuhan, China. Here, the hematological characteristics of patients with severe and critical 2019-nCoV pneumonia in intensive care unit (ICU) were investigated, which may provide the necessary basis for its diagnosis and treatment. METHODS: We collected data on patients with confirmed 2019-nCoV pneumonia in the ICU of Leishenshan Hospital in Wuhan from February 25 to April 2, 2020. Real-time reverse-transcription polymerase chain reaction was used to confirm the presence of 2019-nCoV, and various hematological characteristics were analyzed. RESULTS: All patients tested positive for 2019-nCoV using nasopharyngeal swabs or sputum after admission, and interstitial pneumonia findings were noted on chest computed tomography. Sex, age and comorbidities were not significantly different between the severe and critical groups. In terms of prognosis, the survival rate of patients in the severe group reached 100%, whereas that of patients in the critical group was only 13.33% after positive treatment. Furthermore, lymphocyte percentage, blood urea nitrogen, calcium, D-dimer, myohemoglobin, procalcitonin, and IL-6 levels were high-risk factors for disease progression in critical patients. Finally, lymphocyte percentage and blood urea nitrogen, calcium, myohemoglobin, and IL-6 levels were closely associated with patient prognosis. CONCLUSIONS: 2019-nCoV pneumonia should be considered a systemic disease. Patients with more complications were more likely to develop critical disease. Lymphocyte percentage and blood urea nitrogen, calcium, myohemoglobin, and IL-6 levels can be monitored to prevent progression critical disease.

Th17/Treg cell imbalance plays an important role in respiratory syncytial virus infection compromising asthma tolerance in mice.

Mucosal tolerance is induced early in life and is an important mechanism of protection from diseases, such as asthma. Respiratory syncytial virus (RSV) is a main cause of bronchiolitis and pneumonia in infants. Clinical studies have found that there is a strong association between RSV infection in infancy and later development of asthma, but the underlying mechanisms are unclear. A mouse model of immune tolerance induced by oral feeding of ovalbumin(OVA) was successfully established in our previous studies. We found that RSV infection could break the oral immune tolerance state.RSV infection increased the mRNA expression of IL-17A and IL-17A/Foxp3(the transcription factor forkhead box P3) in OT mice, but the mRNA expression of IL-4 and other T helper(Th)2 cytokines did not change significantly. As detected by flow cytometry analysis, RSV infection elevated Th17 cell levels and correspondingly decreased Regulatory T(Treg) cell levels in the hilar lymph nodes (HLNs) and mesenteric lymph nodes (MLNs), but there were no significant differences in the spleen or peripheral blood.We hypothesized that an imbalance in Th cells played an important role in RSV infection compromising asthma tolerance.RSV infection disrupted asthma tolerance by increasing the Th17/Treg ratio rather than the Th1/Th2 ratio'.Therefore, altering the Th17/Treg ratio has been identified as a potential therapeutic target in asthma caused by RSV or another virus.

Vagal-α7nAChR signaling attenuates allergic asthma responses and facilitates asthma tolerance by regulating inflammatory group 2 innate lymphoid cells.

Disorders of immune tolerance may lead to allergic asthma. Group 2 innate lymphoid cells (ILC2s) and inflammatory ILC2s (iILC2s) are key players in asthma. The vagus nerve innervating the airways releases acetylcholine or neuropeptides (i.e. calcitonin gene-related peptide) via pulmonary C-fibers (PCFs), which could regulate ILC2 activity upon binding the α7 nicotinic acetylcholine receptor (α7nAChR, coded by Chrna7) or neuropeptide receptors. Whether and how α7nAChR and PCFs regulate asthma and the formation of asthma tolerance via ILC2s or iILC2s are poorly understood. We used vagotomized, PCF degeneration and Chrna7 knockout mice to investigate ovalbumin (OVA)-induced asthma and oral OVA feeding-induced asthma tolerance. Our results revealed that vagotomy could generally suppress lung ILC2s and iILC2s, which mitigated allergic asthma responses but disrupted asthmatic tolerance. Removal of neuropeptides by PCF degeneration also reduced lung ILC2s and iILC2s, attenuating asthma responses, but did not affect asthma tolerance. In comparison, deletion of Chrna7 increased resident ILC2s and trafficking iILC2s in the lung, worsened allergic inflammation and disrupted oral tolerance. Mechanistically, deletion of Chrna7 in asthma-tolerant conditions upregulated T helper 2 cytokine- (Il4, Il13 and Il25) and sphingosine-1-phosphate (S1P)-related genes (S1pr1 and Sphk1). Blockade of S1P reduced iILC2 recruitment into asthmatic lungs. Our work is the first to demonstrate that vagal-α7nAChR signaling engaging with iILC2s and S1P not only alleviates asthma but also facilitates asthma tolerance. These findings may provide a novel therapeutic target for attenuating asthma by enhancing asthmatic tolerance.

iNKT cells with high PLZF expression are recruited into the lung via CCL21-CCR7 signaling to facilitate the development of asthma tolerance in mice.

Establishment of immune tolerance is crucial to protect humans against asthma. Promyelocytic leukemia zinc finger (PLZF) is an emerging suppressor of inflammatory responses. CCL21-CCR7 signaling mediates tolerance development. However, whether PLZF and CCL21-CCR7 are required for the development of asthma tolerance is unknown. Here, we found that Zbtb16 (coding PLZF) and Ccl21 were upregulated in OVA-induced asthma tolerance (OT) lungs by RNA-seq. PLZF physically interacted with GATA3 and its expression was higher in GATA3+ Th2 cells and ILC2s in OT lungs. Zbtb16-knockdown in lymphocytes promoted the differentiation of CD3e+ CD4+ T cells, particularly those producing IL-4 and IL-5. Moreover, iNKT cells with high expression of PLZF were recruited into the lungs via draining lymph nodes during tolerance. Blockade of CCL21-CCR7 signaling in OT mice decreased the PLZF+  cell population, abolished CCR7-induced PLZF+ iNKT recruitment to the lungs, enhanced Th2responses and exacerbated lung pathology. In OT mice, respiratory syncytial virus (RSV) infection impeded PLZF+  cell and CCR7+ PLZF+ iNKT cellrecruitment to the lungs and increased airway resistance. Collectively, these results indicate that PLZF could interact with GATA3 and restrain differentiation of IL-4- and IL-5-producing T cells, iNKT cells with high PLZF expression are recruited to the lungs via CCL21-CCR7 signaling to facilitate the development of asthma tolerance.

Astragaloside IV attenuates IL-1ß secretion by enhancing autophagy in H1N1 infection.

Excessive secretion of inflammatory factors (cytokine storm) plays a significant role in H1N1-induced acute pneumonia, and autophagy acts as a cell-intrinsic mechanism to regulate inflammation. Astragaloside IV (AS-IV), originating from the astragalus root, possesses multiple pharmacological activities, such as anti-inflammation. However, the influences of AS-IV on H1N1-induced autophagy and inflammation have remained elusive. It has been reported that H1N1 infection leads to the accumulation of autophagosomes but obstructs autophagosomes incorporating into lysosomes, whereas the present study showed that AS-IV enhanced autophagy activation in H1N1 infection. Furthermore, we found that AS-IV promoted H1N1-triggered formation of autophagosomes and autolysosomes. Additionally, it was noted that AS-IV did not affect viral replication, mRNA level of interleukin-1 beta (IL-1ß) and pro-IL-1ß protein level, but significantly decreased secretion of IL-1ß, and chloroquine (CQ, as an inhibitor of autophagy) increased secretion of IL-1ß in H1N1 infection. In conclusion, AS-IV stimulates the formation of autophagosomes and the fusion of autophagosomes and lysosomes in H1N1 infection and may lead to decreased IL-1ß secretion.

LncRNA SNHG3 is activated by E2F1 and promotes proliferation and migration of non-small-cell lung cancer cells through activating TGF-ß pathway and IL-6/JAK2/STAT3 pathway.

Recently, long noncoding RNAs (lncRNAs) have been widely reported to play pivotal roles in the regulation of human cancers. Although the oncogenic property of lncRNA small nucleolar RNA host gene 3 (SNHG3) has been revealed in a variety of cancers, functions and regulatory mechanism of SNHG3 in non-small-cell lung cancer (NSCLC) remain to be investigated. In this study, we detected the upregulated expression of SNHG3 in NSCLC tissues as well as cells through quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis. Using Kaplan-Meier analysis, we determined that a high-level of SNHG3 was associated with a low overall survival rate of patients with NSCLC. Through gain and loss of function experiments, we demonstrated that SNHG3 had a significantly positive effect on NSCLC cell proliferation and migration. Mechanistic investigations revealed that SNHG3 was a predicted direct transcriptional target of E2F1. We observed that the transcriptional activation of SNHG3 could be induced by E2F1. To explore the mechanism, rescue experiments were carried out, which revealed that the cotreatment with SB-431542, JSI-124, or JSI-124 + SB-431542 rescued the effects brought by the overexpression of SNHG3 on NSCLC cell proliferation, migration, and epithelial-mesenchymal transition process. Our results suggested that E2F1 activated SNHG3 and promoted cell proliferation and migration in NSCLC via transforming growth factor-ß pathway and interleukin-6/janus-activated kinase 2/signal transducer and activator of transcription 3 pathway, which implied that SNHG3 may be a biomarker for the treatment of patients with NSCLC.

Progress and Current Status of Influenza Researches in China.

Influenza pandemics with different extent occur every year in the world. It can cause high morbidity and mortality, arouse fear panic in public, and attract extensive attention worldwide. This paper reviews the research progress in epidemiological characteristics, detection methods, pathogenesis, treatment and prophylactic measures of influenza in China. It will be helpful for us to understand the current situation of influenza.

Post-marketing safety surveillance and reevaluation of Motherwort injection: A clinical study of 10 094 cases.

OBJECTIVE: To investigate the safety profiles of Motherwort injection (MI). METHODS: A multi-center, prospective and drug- derived hospital intensive monitoring method was conducted to assess the safety of MI in real world applications. This study was based on a very large population after the injection was approved and marketed in China. All patients using the injection in participating hospitals were monitored to determine the incidence, pattern, severity and outcome of associated adverse events. RESULTS: The post-marketing surveillance was performed in 10 094 female patients from April to December, 2015. The incidence of adverse drug reactions (ADRs) was 0.79¡ë(8/10 094). Among the 8 patients, the reported adverse events mainly included systemic abnormalities, such as fever, chills and eyelid edema; skin and appendages disorders, such as pruritus and rash; gastrointestinal disorders, such as nausea, abdominal distension and pain; heart rate and rhythm disorders, such as palpitation and increased heart rate. All of these ADRs were mild in severity. CONCLUSION: In this study the ADRs incidence rate of MI is very low, which supports that it is generally safe for use in obstetric and gynecological diseases. However, the total number of 8 ADRs recorded over a relatively short time span seems limited, and the low number of reports could not represent an absolute guarantee of safety.